crossing96/oncoscreening huggingface dataset:
Collagen-rich airway smooth muscle cells are a metastatic niche for tumor colonization in the lung.	Metastases account for the majority of cancer deaths. While certain steps of the metastatic cascade are well characterized, identification of targets to block this process remains a challenge. Host factors determining metastatic colonization to secondary organs are particularly important for exploration, as those might be shared among different cancer types. Here, we showed that bladder tumor cells expressing the collagen receptor, CD167a, responded to collagen I stimulation at the primary tumor to promote local invasion and utilized the same receptor to preferentially colonize at airway smooth muscle cells (ASMCs)-a rich source of collagen III in lung. Morphologically, COL3-CD167a-driven metastatic foci are uniquely distinct from typical lung alveolar metastatic lesions and exhibited activation of the CD167a-HSP90-Stat3 axis. Importantly, metastatic lung colonization could be abrogated using an investigational drug that attenuates Stat3 activity, implicating this seed-and-soil interaction as a therapeutic target for eliminating lung metastasis.	bladder
Prognostic Value of the Neutrophil-to-Lymphocyte Ratio in Nonmuscle-Invasive Bladder Cancer Treated with GreenLight Laser Vaporization.	Objective: An elevated neutrophil-to-lymphocyte ratio (NLR) is significantly associated with poor outcomes in many types of malignancies, including bladder cancer. However, the prognostic value of NLR in patients with nonmuscle-invasive bladder cancer (NMIBC) treated with GreenLight photoselective vaporization of bladder tumor (PVBT) has not been well studied. In this study, we aimed to explore the association between NLR and survival outcomes in patients with NMIBC who underwent PVBT. Materials and methods: We retrospectively investigated 463 patients with NMIBC who underwent PVBT in Tianjin Union Medical center from January 2012 to January 2017. The patients were divided into two groups based on the NLR value (NLR ≥2.5 and NLR <2.5). Overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were determined using Kaplan-Meier analysis and the log-rank test. Results: Among 463 patients, age, tumor size, tumor focality, tumor grade, or tumor stage in the two groups did not differ significantly. The median follow-up was 40 months (range, 15-60). Thirty-eight patients (8.2%) died of any cause; 24 (5.2%) patients died of bladder cancer. In addition, 88 (19.0%) patients experienced disease recurrence. Elevated NLR was significantly associated with poor OS (χ(2) = 7.457, p = 0.002), CSS (χ(2) = 6.242, p = 0.012), and RFS (χ(2) = 5.372, p = 0.020) in patients with NMIBC who underwent PVBT. Conclusions: Elevated preoperative NLR was significantly associated with poor OS, CSS, and RFS, and it could be considered as an effective and convenient prognostic biomarker for patients with NMIBC who were treated with PVBT.	bladder
Health-related quality of life around the time of diagnosis in patients with bladder cancer.	OBJECTIVES: To quantify the health-related quality of life (HRQoL) of patients with bladder cancer around the time of diagnosis and to test the hypotheses of a two-factor model for the HRQoL questionnaire QLQ-C30. METHODS: From participants in the Bladder Cancer Prognoses Programme, a multicentre cohort study, sociodemographic data were collected using semi-structured face-to-face interviews. Answers to the QLQ-C30 were transformed into a scale from 0 to 100. HRQoL data were analysed in multivariate analyses. The hypothesized two-factor (Physical and Mental Health) domain structure of the QLQ-C30 was also tested with confirmatory factor analyses (CFA). RESULTS: A total of 1160 participants (78%) completed the questionnaire after initial visual diagnosis and before pathological confirmation. Despite non-muscle-invasive bladder cancer (NMIBC) being associated with a higher HRQoL than carcinoma invading bladder muscle, only the domain Role Functioning was clinically significantly better in patients with NMIBC. Age, gender, bladder cancer stage and comorbidity all had a significant influence on QLQ-C30 scores. The CFA showed an overall good fit of the hypothesized two-factor model. CONCLUSION: This study identified a baseline reference value for HRQoL for patients with bladder cancer, which allows better evaluation of any changes in HRQoL as disease progresses or after treatment. In addition, a two-factor (Physical and Mental Health) model was developed for the QLQ-C30.	bladder
Cancer-associated fibroblasts promote cisplatin resistance in bladder cancer cells by increasing IGF-1/ERβ/Bcl-2 signalling.	While cancer-associated fibroblasts (CAFs) in the tumour microenvironment may play important roles in bladder cancer (BCa) progression, their impacts on BCa chemoresistance remain unclear. Using human BCa samples, we found that tumour tissues possessed more CAFs than did adjacent normal tissues. Both the presence of CAFs in the BCa stroma and the expression of ERβ in BCa contribute to chemoresistance, and CAFs and BCa cells interact to affect ERβ expression. In vitro co-culture assays demonstrated that compared with normal bladder cells, BCa cells had a higher capacity to induce the transformation of normal fibroblasts into CAFs. When BCa cells were co-cultured with CAFs, their viability, clone formation ability and chemoresistance were increased, whereas their apoptotic rates were downregulated. Dissection of the mechanism revealed that the recruited CAFs increased IGF-1/ERβ signalling in BCa cells, which then led to the promotion of the expression of the anti-apoptotic gene Bcl-2. Blocking IGF-1/ERβ/Bcl-2 signalling by either an shRNA targeting ERβ or an anti-IGF-1 neutralizing antibody partially reversed the capacity of CAFs to increase BCa chemoresistance. The in vivo data also confirmed that CAFs could increase BCa cell resistance to cisplatin by increasing ERβ/Bcl-2 signalling. The above results showed the important roles of CAFs within the bladder tumour microenvironment, which could enhance BCa chemoresistance.	bladder
Impact of Anaesthetist Volume on Radical Cystectomy Outcomes.	BACKGROUND: Radical cystectomy (RC) is a gold standard treatment for aggressive bladder cancer. Higher surgical volumes through centralisation are associated with improved RC outcomes. The impact of anaesthetist experience and RC volume on outcomes is less clear. OBJECTIVE: We sought to examine RC outcomes stratified by anaesthetist volume using a contemporary homogenous series. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of a prospectively collected, single-surgeon database of RC patients over a 10-yr period. INTERVENTION: Four hundred and fifty-three consecutive patients underwent RC, including 430 (95%) with anaesthetist annotation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Anaesthetists were stratified into low- (<10 cases) and high-volume (≥10 cases) classes. Primary outcomes were blood loss, transfusion rates, length of stay (LOS), and postoperative mortality. RESULTS AND LIMITATIONS: In total, 63 anaesthetists were included for analysis (median two RCs per anaesthetist). Of 63 anaesthetists, 56 (88.9%) and seven (11.1%) were classified, respectively, into low and high volume, and these provided cover for 110 (25.6%) and 320 (74.4%) patients, respectively. When comparing high- versus low-volume anaesthetists, there were shorter LOS (median [interquartile range {IQR}]: 10 [6-14] vs 12 [7-19] d, p =  0.008), lower blood loss (median [IQR]: 600 [384-1000] vs 800 [500-1275] ml, p<0.001), and lower transfusion rate (23/320, 7.2% vs 22/110, 20%; p <  0.001). There was no difference in disease-specific mortality, overall mortality, or readmission rates. In multivariable analysis, a high anaesthetist volume was independently associated with transfusion rate (odds ratio 0.24 [0.07-0.83], p =  0.02). CONCLUSIONS: Higher-volume anaesthetists have lower transfusion rates for RC patients. Whilst LOS and blood loss may also differ with experience, there is no difference in mortality after RC. PATIENT SUMMARY: Radical cystectomy is a major operation. Experienced anaesthetists give fewer blood products to patients undergoing this operation. They may also help reduce blood loss and speed recovery. However, all other recovery measures were similar.	bladder
Circular RNA hsa_circ_0075828 promotes bladder cancer cell proliferation through activation of CREB1.	Circular RNAs (circRNAs), one kind of non-coding RNA, have been reported as critical regulators for modulating gene expression in cancer. In this study, microarray analysis was used to screen circRNA expression profiles of bladder cancer (BC) 5637 cells, T24 cells and normal control SV-HUC-1 cells. The data from the microarray showed that hsa_circ_0075828 (named circCASC15) was most highly expressed in 5637 and T24 cells. circCASC15 was highly expressed in BC tissues and cells. Overexpression of circCASC15 was closely associated with BC tumor stage and promoted cell proliferation significantly in vitro and in vivo. Mechanistically, circCASC15 could act as miR-1224-5p sponge to activate the expression of CREB1 to promote cell proliferation in BC. In short, circCASC15 promotes cell proliferation in BC, which might be a new molecular target for BC diagnosis and therapy. [BMB Reports 2020; 53(2): 82-87].	bladder
miR-30e-5p suppresses cell proliferation and migration in bladder cancer through regulating metadherin.	Recent studies have suggested that miR-30e-5p is dysregulated in several human carcinomas; however, the mechanism of miR-30e-5p in bladder cancer (BCa) remains unknown. Here, we confirmed that the expression of miR-30e-5p was decreased in human BCa specimens and cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Upregulation of miR-30e-5p decreased the proliferation and migration in T24 and UM-UC-3 cells. Metadherin (MTDH) was a potential target for miR-30e-5p through bioinformatics analysis. Dual-luciferase assays were conducted to validate the interaction between miR-30e-5p and MTDH, which demonstrates that the relative luciferase activity was significantly downregulated after transfected miR-30e-5p mimic compared with control mimic in 293T cells. We also detected that whether silencing of MTDH by using small interfering(si)-MTDH matched effects caused by miR-30e-5p overexpression in BCa cells lines by Cell Counting Kit-8 (CCK-8), colony formation, and transwell assay, and we found the effects of silencing of MTDH same as miR-30e-5p overexpression. Furthermore, we verified that the restoration of MTDH in miR-30e-5p-overexpressed BCa cells rescued the inhibitory effects of miR-30e-5p. In conclusion, these results demonstrated that miR-30e-5p may inhibit BCa cells growth and invasiveness by targeting MTDH and may be a promising therapeutic agent for treating clinical BCa patients.	bladder
A Rare Case of Granulomatous Pneumonitis Due to Intravesical BCG for Bladder Cancer.	Granulomatous pneumonitis is a rare complication of bacillus Calmette-Guerin immunotherapy following intravesical administration of bacillus Calmette-Guerin. The authors present an unusual case of a 67-year-old man who developed mild and non-specific symptoms, following intravesical bacillus Calmette-Guerin instillations. Examinations revealed features of miliary tuberculosis and granuloma suggestive of mycobacterial infection. Anti-tuberculosis treatment resulted in a remarkable improvement in his symptoms and gradually upgrading of radiological appearance. The symptoms were less severe than some others described but this case provides evidence that, even in some cases, specific treatment may be necessary. We highlight the importance of recognizing miliary Mycobacterium bovis as a probable complication of bacillus Calmette-Guerin immunotherapy. The clinical disease course can be mild, despite extensive bilateral miliary nodules on primary presentation.	bladder
Synergistic antitumour effects of triptolide plus 10-hydroxycamptothecin onbladder cancer.	BACKGROUND: Hydroxycamptothecin (HCPT) is used as a clinical chemotherapy regimen to treat bladder cancer, but more efficacious novel combination treatments are needed. METHODS: Cultured bladder cancer cell lines EJ and UMUC3 were treated with triptolide (TPL) and/or HCPT. A flow cytometry approach was used to detect cell cycle phase, apoptosis and reactive oxygen species. Western blotting was used to measure CDK4, CDK6, CyclinD1, catalase, Caspase8 and Bcl-xl protein levels in control, TPL treatment, HCPT treatment and TPL plus HCPT treatment bladder cancer cells. AKT pathway proteins, including AKT and p-AKT, were also detected by western blotting. UMUC3 cells treated with DMSO, HCPT, TPL and HCPT plus TPL were injected subcutaneously into mice (n = 3 per group). RESULTS: The flow cytometry and western blot results indicated that compared to TPL or HCPT treatment alone, combination treatment of HCPT and TPL significantly induced cell cycle arrest at the G1 phase via suppressing CDK4, CDK6 and CyclinD1 in the EJ and UMUC3 bladder cancer cell lines. HCPT and TPL combination treatment also significantly increased the apoptosis rate and apoptosis-related protein levels (Caspase8 and Bcl-xl). Levels of the AKT pathway-related proteins AKT/p-AKT were significantly lower in EJ and UMUC3 cells treated with TPL and UMUC3 than in those cells treated with TPL or HCPT alone. TPL plus HCPT treatment significantly reduced bladder tumour sizes in vivo on the seventh and tenth days. CONCLUSIONS: Compared to TPL or HCPT treatment alone, TPL plus HCPT combination treatment had significantly better anticancer effects.	bladder
The Impact of Omission of Intraoperative Frozen Section Prior to Orthotopic Neobladder Reconstruction.	PURPOSE: Current guidelines recommend confirming a negative urethral margin prior to orthotopic neobladder reconstruction. We investigated our rate of urethral positive margins and recurrence in the absence of intraoperative frozen section. MATERIALS AND METHODS: We retrospectively reviewed clinical and pathological data on 357 patients who underwent radical cystectomy and orthotopic urinary diversion without intraoperative frozen section. At a median followup of 27 months the rates of positive urethral margins and urethral recurrence were tabulated. Differences in overall and recurrence-free survival in patients with a positive urethral margin were analyzed by Cox regression to generate the HR with the 95% CI. RESULTS: We identified 6 urethral recurrences (1.6%) during followup. The urethral recurrence rate was not higher in patients with a positive urethral margin (p=0.22). In the 15 patients with positive urethral margins overall survival was unchanged (HR 0.98, 95% CI 0.24-4.04). When accounting for lymph node staging, recurrence-free survival was not significantly worse in patients with positive urethral margins (HR 2.33, 95% CI 0.95-5.73). CONCLUSIONS: Omitting intraoperative frozen section prior to orthotopic neobladder reconstruction appears safe with a rate of urethral recurrence similar to that in historical series. It may allow for increased performance of orthotopic urinary diversions.	bladder
Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by Ultra-Deep Sequencing of Plasma Cell-Free DNA in Patients With Urothelial Bladder Carcinoma.	PURPOSE: Novel sensitive methods for early detection of relapse and for monitoring therapeutic efficacy may have a huge impact on risk stratification, treatment, and ultimately outcome for patients with bladder cancer. We addressed the prognostic and predictive impact of ultra-deep sequencing of cell-free DNA in patients before and after cystectomy and during chemotherapy. PATIENTS AND METHODS: We included 68 patients with localized advanced bladder cancer. Patient-specific somatic mutations, identified by whole-exome sequencing, were used to assess circulating tumor DNA (ctDNA) by ultra-deep sequencing (median, 105,000×) of plasma DNA. Plasma samples (n = 656) were procured at diagnosis, during chemotherapy, before cystectomy, and during surveillance. Expression profiling was performed for tumor subtype and immune signature analyses. RESULTS: Presence of ctDNA was highly prognostic at diagnosis before chemotherapy (hazard ratio, 29.1; P = .001). After cystectomy, ctDNA analysis correctly identified all patients with metastatic relapse during disease monitoring (100% sensitivity, 98% specificity). A median lead time over radiographic imaging of 96 days was observed. In addition, for high-risk patients (ctDNA positive before or during treatment), the dynamics of ctDNA during chemotherapy was associated with disease recurrence (P = .023), whereas pathologic downstaging was not. Analysis of tumor-centric biomarkers showed that mutational processes (signature 5) were associated with pathologic downstaging (P = .024); however, no significant correlation for tumor subtypes, DNA damage response mutations, and other biomarkers was observed. Our results suggest that ctDNA analysis is better associated with treatment efficacy compared with other available methods. CONCLUSION: ctDNA assessment for early risk stratification, therapy monitoring, and early relapse detection in bladder cancer is feasible and provides a basis for clinical studies that evaluate early therapeutic interventions.	bladder
Role of feline sarcoma‑related protein in the viability and apoptosis of bladder cancer cells.	Feline sarcoma‑related protein (Fer) is a type of nuclear and cytoplasmic non‑receptor protein tyrosine kinase, which is associated with the progression of numerous types of cancer. Previously, we identified that Fer is associated with the migration and invasion of bladder cancer. The present study aimed to investigate the role of Fer in bladder cancer cell viability and apoptosis. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were performed to detect the expression levels of Fer; short interference RNA (siRNA) and overexpression vectors were used to downregulate or upregulate Fer expression, respectively. The effects on cell proliferation ability and cell apoptosis were then tested by MTT assay and flow cytometry. The results revealed that Fer expression was upregulated in bladder cancer cell lines. Downregulation of Fer expression by siRNA significantly suppressed T24 cell viability and induced apoptosis, as well as inducing cell cycle arrest. Conversely, Fer overexpression in 5637 cells significantly promoted cell viability and cell cycle progression, but inhibited cell apoptosis. Furthermore, the suppression and overexpression of Fer significantly altered the expression of cleaved caspase‑3 and Bcl‑2, and dysregulated the P38 mitogen‑activated protein kinase signaling pathway. The findings of the present study indicate a possible molecular mechanism of Fer in bladder cancer and may be considered as a potential target in the treatment of this disease.	bladder
Molecular subtypes applied to a population-based modern cystectomy series do not predict cancer-specific survival.	OBJECTIVES: To investigate the preoperative prognostic value of molecular subtypes in relation to clinical information, histopathological findings, and molecular markers for patients with bladder cancer treated with radical cystectomy. PATIENTS AND METHODS: After standard preoperative staging, a population-based cohort of 519 patients underwent radical cystectomy between 2006 and 2011. Following pathological review of all transurethral resection of bladder tumor specimens, tissue microarrays were constructed, and RNA was extracted from formalin-fixed tissue blocks. Immunohistochemistry (IHC) was performed using markers suggested to be relevant for prognosis (ZEB2, CCND1, CD3, CD68, CDH3, HER3, KRT14, CDKN2A(p16), TP63, FGFR3, EPCAM, GATA3, FOXA1, ERBB2, and EGFR). IHC- and gene-expression-based molecular classification was also conducted. Univariate and multivariate Cox proportional hazards regression were used for survival analyses. RESULTS: Clinical T3 stage (Hazard Ratio [HR] 1.6, Confidence Interval [CI] 1.1-2.3), hydronephrosis (HR 1.7, CI 1.2-2.3), lymphovascular invasion (LVI) (HR 2.6, CI 1.9-3.6), extensive necrosis (HR 1.6, CI 1.1-2.5), and CD68/CD3-ratio >1 (HR 1.3, CI 1.1-1.5) in the transurethral resection of bladder tumor specimen was associated with worse cancer-specific survival (CSS) and progression-free survival (data not shown). In multivariate analysis, higher clinical T stage (HR 1.3, CI 1.1-1.7; P = 0.007) and presence of LVI (HR 2.4, CI 1.7-3.5; P = 1.8 × 10(-)(6)) were associated with worse CSS, whereas only LVI was associated with progression-free survival. Molecular subtypes (assessed by Lund taxonomy and the Consensus molecular subtypes of muscle-invasive bladder cancer) and published single IHC markers were not associated with survival. CONCLUSIONS: In the present large population-based cystectomy series, LVI and clinical stage were independently associated with CSS. However, molecular subtypes determined by global gene expression showed no such association with CSS according to either the Consensus molecular subtypes of muscle-invasive bladder cancer or Lund taxonomy.	bladder
Plasmacytoid/diffuse urothelial carcinoma: a single-institution immunohistochemical and molecular study of 69 patients.	Accurate diagnosis of plasmacytoid urothelial carcinoma (PUC) is important given its poor prognosis and frequent presentation at high stage. We aim to assess the clinicopathological features, molecular aberrations, and follow-up data in a series of PUC cases from a single tertiary cancer center. Seventy-two urinary bladder, ureteral, and renal pelvic specimens with urothelial carcinoma with plasmacytoid differentiation were identified. Immunohistochemical stains were performed on 48 cases. Among urinary bladder origin markers, GATA3 was most sensitive (96%). Breast carcinoma markers (estrogen receptor, mammaglobin) were usually negative, but progesterone receptor stained 1 case (4%). Neuroendocrine markers CD56 and TTF-1 were each positive in 1 case (4% and 4%, respectively). Gastrointestinal adenocarcinoma marker CDX2 was positive in 4 cases (15%), but nuclear β-catenin was negative in all cases. CD138 was positive in 83% and E-cadherin expression was lost in 57% of cases. Fluorescence in situ hybridization using the UroVysion Bladder Cancer Kit and FGFR3 mutational analysis using polymerase chain reaction were performed on 15 cases; deletion of chromosome 9p21 was common (60%), and FGFR3 mutations were detected in 60% of cases (5 cases had both deletion 9p21 and FGFR3 mutations). Cases were divided into 3 morphologic groups: classic (29%), desmoplastic (35%), and pleomorphic (36%). The 3 morphologic subtypes had distinct survival outcomes (P = .083), with median survival for all patients 18 being months versus 10 months for the desmoplastic group.	bladder